The proposed research will define the mechanisms of interactions between platelets and endotoxins isolated and purified from a number of gram negative bacteria which result in either complement-mediated lysis or noncytolytic secretion. The membrane receptor responsible for binding the lipid A and/or lipid A-associated protein will be isolated and characterized. The molecular mechanism of processing of lipid A by the platelet membrane which results in the ability of the platelet to undergo a secretory response upon subsequent addition of calcium will be defined. Experiments will critically evaluate the capacity of a spectrum of endotoxins to induce alterations in human platelets in order to assess the potential contribution of these cells to the pathophysiology of endotoxin shock.